Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA (cytosine-5)-methyltransferase 3A

Gene

Dnmt3a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Can actively repress transcription through the recruitment of HDAC activity (By similarity).By similarity

Catalytic activityi

S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.PROSITE-ProRule annotation

Enzyme regulationi

Activated by binding to the regulatory factor DNMT3L.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei660 – 6601S-adenosyl-L-methionineBy similarity
Active sitei706 – 7061PROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri489 – 51931GATA-type; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri530 – 58657PHD-type; atypicalPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • chromatin binding Source: RGD
  • DNA (cytosine-5-)-methyltransferase activity Source: UniProtKB
  • DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Source: RGD
  • DNA binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • unmethylated CpG binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • C-5 methylation of cytosine Source: GOC
  • cellular response to amino acid stimulus Source: Ensembl
  • cellular response to ethanol Source: RGD
  • cellular response to hypoxia Source: RGD
  • DNA methylation Source: UniProtKB
  • DNA methylation involved in embryo development Source: Ensembl
  • DNA methylation involved in gamete generation Source: Ensembl
  • DNA methylation on cytosine Source: RGD
  • DNA methylation on cytosine within a CG sequence Source: RGD
  • hepatocyte apoptotic process Source: RGD
  • hypermethylation of CpG island Source: Ensembl
  • methylation-dependent chromatin silencing Source: Ensembl
  • mitotic cell cycle Source: RGD
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • neuron differentiation Source: RGD
  • positive regulation of cell death Source: RGD
  • regulation of gene expression by genetic imprinting Source: Ensembl
  • response to antidepressant Source: RGD
  • response to cocaine Source: RGD
  • response to drug Source: RGD
  • response to estradiol Source: RGD
  • response to ethanol Source: RGD
  • response to ionizing radiation Source: RGD
  • response to lead ion Source: RGD
  • response to nutrient levels Source: RGD
  • response to toxic substance Source: RGD
  • response to vitamin A Source: RGD
  • S-adenosylhomocysteine metabolic process Source: RGD
  • S-adenosylmethioninamine metabolic process Source: RGD
  • spermatogenesis Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Repressor, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

ReactomeiREACT_280832. PRC2 methylates histones and DNA.
REACT_287764. DNA methylation.
REACT_338782. RMTs methylate histone arginines.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA (cytosine-5)-methyltransferase 3A (EC:2.1.1.37)
Short name:
Dnmt3a
Gene namesi
Name:Dnmt3a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi1303336. Dnmt3a.

Subcellular locationi

GO - Cellular componenti

  • chromosome, centromeric region Source: Ensembl
  • cytoplasm Source: UniProtKB
  • euchromatin Source: UniProtKB
  • nuclear heterochromatin Source: Ensembl
  • nuclear matrix Source: UniProtKB
  • nucleoplasm Source: Ensembl
  • nucleus Source: UniProtKB
  • XY body Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 908908DNA (cytosine-5)-methyltransferase 3APRO_0000313030Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei102 – 1021PhosphoserineBy similarity
Modified residuei239 – 2391PhosphoserineBy similarity
Modified residuei251 – 2511PhosphoserineBy similarity
Modified residuei257 – 2571PhosphothreonineBy similarity

Post-translational modificationi

Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ1LZ53.

PTM databases

PhosphoSiteiQ1LZ53.

Expressioni

Gene expression databases

GenevisibleiQ1LZ53. RN.

Interactioni

Subunit structurei

Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) (By similarity). Interacts with DNMT1 and DNMT3B. Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain (By similarity). Interacts with the PRC2/EED-EZH2 complex (By similarity). Interacts with UBC9, PIAS1 and PIAS2 (By similarity). Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). Interacts with UHRF1 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000046524.

Structurei

3D structure databases

ProteinModelPortaliQ1LZ53.
SMRiQ1LZ53. Positions 279-420, 623-908.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini257 – 31559PWWPPROSITE-ProRule annotationAdd
BLAST
Domaini478 – 610133ADDPROSITE-ProRule annotationAdd
BLAST
Domaini630 – 908279SAM-dependent MTase C5-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni195 – 399205Interaction with DNMT1 and DNMT3BBy similarityAdd
BLAST
Regioni490 – 58293Interaction with the PRC2/EED-EZH2 complexBy similarityAdd
BLAST
Regioni637 – 6415S-adenosyl-L-methionine bindingBy similarity
Regioni682 – 6843S-adenosyl-L-methionine bindingBy similarity
Regioni887 – 8893S-adenosyl-L-methionine bindingBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi479 – 52749Cys-richAdd
BLAST

Domaini

The PWWP domain is essential for targeting to pericentric heterochromatin.

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.PROSITE-ProRule annotation
Contains 1 ADD domain.PROSITE-ProRule annotation
Contains 1 GATA-type zinc finger.PROSITE-ProRule annotation
Contains 1 PHD-type zinc finger.PROSITE-ProRule annotation
Contains 1 PWWP domain.PROSITE-ProRule annotation
Contains 1 SAM-dependent MTase C5-type domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri489 – 51931GATA-type; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri530 – 58657PHD-type; atypicalPROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG70699.
GeneTreeiENSGT00390000008341.
HOGENOMiHOG000230875.
HOVERGENiHBG051381.
InParanoidiQ1LZ53.
KOiK17398.
OMAiYTEMWVE.
OrthoDBiEOG7MWGW6.
PhylomeDBiQ1LZ53.
TreeFamiTF329039.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR030487. DNMT3A.
IPR000313. PWWP_dom.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR23068:SF10. PTHR23068:SF10. 1 hit.
PfamiPF00855. PWWP. 1 hit.
[Graphical view]
SMARTiSM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS50812. PWWP. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

Isoform 1 (identifier: Q1LZ53-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPSSGPGDTS ISSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR
60 70 80 90 100
KRKHPPVESS DTPKDPAVTT KSQPTAQDSG PSDLLPNGDL EKRSEPQPEE
110 120 130 140 150
GSPAAGQKGG APAEGEGTET PPEASRAVEN GCCVTKEGRG ASAGEGKEQK
160 170 180 190 200
QTNIESMKME GSRGRLRGGL GWESSLRQRP MPRLTFQAGD PYYISKRKRD
210 220 230 240 250
EWLARWKREA EKKAKVIAVM NAVEESQASG ESQKVEEASP PAVQQPTDPA
260 270 280 290 300
SPTVATTPEP VGADAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS
310 320 330 340 350
WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF
360 370 380 390 400
HQATYNKQPM YRKAIYEVLQ VASSRAGKLF PACHDSDESD TGKAVEVQNK
410 420 430 440 450
QMIEWALGGF QPSGPKGLEP PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA
460 470 480 490 500
KKPRKSTTEK PKVKEIIDER TRERLVYEVR QKCRNIEDIC ISCGSLNVTL
510 520 530 540 550
EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR EVLMCGNNNC
560 570 580 590 600
CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR
610 620 630 640 650
LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG
660 670 680 690 700
IQVDRYIASE VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV
710 720 730 740 750
IGGSPCNDLS IVNPARKGLY EGTGRLFFEF YRLLHDARPK EGDDRPFFWL
760 770 780 790 800
FENVVAMGVS DKRDISRFLE SNPVMIDAKE VSAAHRARYF WGNLPGMNRP
810 820 830 840 850
LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK DQHFPVFMNE
860 870 880 890 900
KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP

LKEYFACV
Length:908
Mass (Da):101,669
Last modified:May 30, 2006 - v1
Checksum:i6CCE9EB4E9CEB409
GO
Isoform 2 (identifier: Q1LZ53-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-219: Missing.

Show »
Length:689
Mass (Da):77,825
Checksum:i1C75674CFC1C97BE
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 219219Missing in isoform 2. 1 PublicationVSP_029986Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BN000395 mRNA. Translation: CAE52317.1.
BN000396 mRNA. Translation: CAE52318.1.
RefSeqiNP_001003957.1. NM_001003957.1. [Q1LZ53-2]
NP_001003958.1. NM_001003958.1. [Q1LZ53-1]
XP_008762753.1. XM_008764531.1. [Q1LZ53-2]
UniGeneiRn.92659.

Genome annotation databases

EnsembliENSRNOT00000047210; ENSRNOP00000046524; ENSRNOG00000026649. [Q1LZ53-1]
ENSRNOT00000089093; ENSRNOP00000069441; ENSRNOG00000026649. [Q1LZ53-2]
GeneIDi444984.
KEGGirno:444984.

Keywords - Coding sequence diversityi

Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BN000395 mRNA. Translation: CAE52317.1.
BN000396 mRNA. Translation: CAE52318.1.
RefSeqiNP_001003957.1. NM_001003957.1. [Q1LZ53-2]
NP_001003958.1. NM_001003958.1. [Q1LZ53-1]
XP_008762753.1. XM_008764531.1. [Q1LZ53-2]
UniGeneiRn.92659.

3D structure databases

ProteinModelPortaliQ1LZ53.
SMRiQ1LZ53. Positions 279-420, 623-908.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000046524.

PTM databases

PhosphoSiteiQ1LZ53.

Proteomic databases

PaxDbiQ1LZ53.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000047210; ENSRNOP00000046524; ENSRNOG00000026649. [Q1LZ53-1]
ENSRNOT00000089093; ENSRNOP00000069441; ENSRNOG00000026649. [Q1LZ53-2]
GeneIDi444984.
KEGGirno:444984.

Organism-specific databases

CTDi1788.
RGDi1303336. Dnmt3a.

Phylogenomic databases

eggNOGiNOG70699.
GeneTreeiENSGT00390000008341.
HOGENOMiHOG000230875.
HOVERGENiHBG051381.
InParanoidiQ1LZ53.
KOiK17398.
OMAiYTEMWVE.
OrthoDBiEOG7MWGW6.
PhylomeDBiQ1LZ53.
TreeFamiTF329039.

Enzyme and pathway databases

ReactomeiREACT_280832. PRC2 methylates histones and DNA.
REACT_287764. DNA methylation.
REACT_338782. RMTs methylate histone arginines.

Miscellaneous databases

NextBioi697058.
PROiQ1LZ53.

Gene expression databases

GenevisibleiQ1LZ53. RN.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR030487. DNMT3A.
IPR000313. PWWP_dom.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR23068:SF10. PTHR23068:SF10. 1 hit.
PfamiPF00855. PWWP. 1 hit.
[Graphical view]
SMARTiSM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS50812. PWWP. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci."
    Lees-Murdock D.J., McLoughlin G.A., McDaid J.R., Quinn L.M., O'Doherty A., Hiripi L., Hack C.J., Walsh C.P.
    Genomics 84:193-204(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).

Entry informationi

Entry nameiDNM3A_RAT
AccessioniPrimary (citable) accession number: Q1LZ53
Secondary accession number(s): Q1LZ52
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: May 30, 2006
Last modified: July 22, 2015
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.